"Irish Jimmy" Duhig and his Uisce Beatha : Penicillin as Orange Juice

I woke up the middle of last night to find I had a bad cold and so naturally got to thinking about its prevention and cure.

Its natural and unnatural cure and what all this had to do with the unknown history of wartime's crude penicillin.

Crude Penicillin and Bacterial Transformation : two neologisms of Henry Dawson

Henry Dawson was far from a wordsmith but he did coin two neologisms that have survived in today's scientific and historical lexicon.

One was "bacterial transformation" (a form of HGT, horizontal gene transfer -- basically non-Darwinian inheritance) and the other was "crude penicillin".

To explain this latter term is is best to recognize it is really a term of scientific and political polemics.

Let us imagine a British Empire in the early 1940s, badly hurting a time of war because it had refused to accept a fact known for at least two centuries.

That fact was that the most natural , most versatile and cheapest way to solve the naval and merchant ship scurvy crisis was with a good supply of citrus fruit kept on board.

Marshalled against this fact discovered by James Lind was an array of louder, better educated and greedier voices.

What they were telling the government and the media and future historians was that Britain's dying sailors must simply be patient.

In its own sweet time an expensive synthetic vitamin C was sure to emerge, fully patented, from one of the nation's chemical firms.

One expensively patented , tasteless , pill would solve the human daily needs for vitamin C - as would other patented pills for all our daily food intake.

We needn't waste time away from our desks on meals when a glass of water and a big handful or two of pills would solve the problem.

Against this chemical boasting would be an array of people saying that they looked forward to meals - perhaps even more than sex and certainly far more than they looked forward to work.

Others would point out that citrus fruit and vitamin C rich vegetables are found world wide - are both cheap and abundant - a security of supply issue.

They would further point out that the deadly delay in solving this sea-going crisis for the Empire was simply down to greed and ambition.

The delay was down to some ambitious scientists seeking the glory for having synthesized something Mother Nature already provided and to some greedy chemical companies wanting a profitable patent to exploit.

These claims against patented vitamin C pills are so damning  a master scientific polemist would be called upon to defend Chemistry.

A scientific polemist like Howard Florey because he, too, was a bit of a neologism creator : he was the first person to talk about impure and pure penicillin, for example.

An orange ,he could point out, could potentially be a dangerous source of vitamin C because it was an impure  source of the needed vitamin (in the sense that vitamin C only made up a tiny fraction of one percent of the orange by weight).

In a 1940s culture where the middle class had more education than common sense, this would be effective arguing : everyone wanted cleanliness and purity.

Henry Dawson immediately caught onto this "Only I know how to make pure safe penicillin" line of attack from Florey's very first article on penicillin and quickly mounted a rebuttal.

And he did so in the august pages of the New York Times on May 6th 1941.

In effect, he said an orange can be one of four things, as regards to being an safe source of vitamin C.

It could be unsafe because both the orange and its vitamin C are potentially dangerous.

It could be safe because both the orange and its vitamin C are harmless to consume.

It could be unsafe because vitamin C is potentially dangerous, perhaps in larger quantities.

It could be unsafe because the orange itself was potentially toxic.

The only thing to do , as always , was less talk and more experiments.

He tested impure penicillin (penicillium juice) upon himself and upon some human patients and found it perfectly safe.

He boldly called his successful medicine "crude penicillin" --- naturally made penicillin happily bathing its its naturally produced impure bath.

it was a medicine made by microbes and offered up to all, free in the Public Domain : thus meeting Florey's subtle corporate agenda head-on.

Ironically, years later, it was revealed that pure penicillin itself  was potentially unsafe (unlike the rest of the harmless penicillium juice) because when pure it can be given in large enough amounts to result in sudden penicillin allergy deaths !

Pure members of the aryan races might still believe they can only survive on pure penicillin and pure vitamin C but the rest of this polyglot world still likes to take its daily nourishment 'crude' , dining around the table with family and friends.

It hasn't seemed to harm the seven billions of us so far....

Fleming's seminal 1929 article on penicillin is missing two words : impurities and crude

Fleming, in this extremely famous article, defines his "penicillin" as consisting of  one or more soluble solid active ingredients in a liquid nutritional  broth, no more and no less.

He makes it clear that "penicillin" is merely a useful shorthand for that cumbersome longer phrase.

He never once uses the word impurities or impure or crude: to him his active ingredient is perhaps ALL  of the soluble solids left behind when the water is evaporated .

Fleming says that this (mixture) of soluble solids and nutritional broth is non-toxic to the extent that it can be injected in a mass of one fortieth of body weight without harm.

(That is, this liquid mixture appears to be safely injectable in a mouse and a rabbit to the equivalent of  a single bolus of 1500 to 2000 cc into an average adult human.)

And Fleming isn't the only one never to use impurities or crude in describing penicillin in a scientific report, in the twelve years between 1928 and 1940.

Clutterbuck & Raistrick in 1932 do not use the words impurities or crude, nor does Roger Reid in 1934, or Elizabeth Pickering at Squibb in 1937 or Siegbert Bornstein in 1939.

But Howard Florey, the chemist manque , the anti-clinician, he sure does in 1940.

He might even ask his potential readers, "Purity : how many ways do you want it ?"

Despite being a very short article - almost more of a scientific note  in the style of letters to the journal Nature - Florey manages to inject the words "purify" , "not a pure substance", "impure" and "impurities" and talks constantly of his "penicillin preparations" as if they are something quite different and advanced from Fleming's liquid penicillin.

But, in fact, Florey has merely concentrated all the soluble solids by evaporating away the water, so that 4 tiny units of anti-bacterial activity are no longer in a gram of water and solubles, but in a milligram of solubles.

But two thirds of the scarce anti-bacterial activity has been lost in this totally unnecessary and expensive and complex effort : and in any case, this dry powder has to have water added back into it, to inject it for use !

Dawson, Pulvertaft, Duhig, Yermolieva , Berger (among a mere handful of all the world's doctors ---- maybe just .01% of them  thought this way) seemed to have picked up on Fleming's crucial point.

A point he quickly missed, because he publicly always said that the substance would have to be synthesized pure by chemists before it might be a useful antiseptic .

But his original point was true, nevertheless.

It was this : that regardless of whatever was the compound(s) with that mixture of soluble solids that had the anti-bacterial powers, the water and other solids had no harmful effect and needn't be laboriously purified out - or even concentrated by evaporation - at a tremendous loss of the anti-bacterial matter.

Dawson is at pains to introduce the word "crude" repeatedly in his 1941 article, but with a much different point that Florey's article a few months earlier.

Dawson wants to hammer home that despite the crudity of this mixture of the anti-bacterial activity and the other soluble solids, it was still non-toxic even when injected ( finally) into the human blood stream : life-saving does not have to wait until the chemist's apple has been polished to a 't' .

Dawson is , in a sense , "The James Lind of Penicillin".

Put in another way, James Lind said we don't know which compound (later determined to be vitamin c) it is in limes that prevents scurvy but that shouldn't stop us from using it - NOW ! - to save lives.

Almost two hundred years later, another Scottish (Canadian) doctor (Henry Dawson) said pretty much the same thing.

The lesson might be this : chemists, let the sleeping dogs of chemical perfection lie -----  while we clinicians get on with saving lives.....

Vitamin C pills vs oranges: a metaphor for the dueling penicillin of Aussie docs, Florey and Duhig

A nice big fresh juicy orange and a tiny white pill can both have the exact same amount of vitamin c in them : about 100 mg ,  just above the recommended daily intake of the vitamin for a adult.

The synthetic vitamin c pill (first invented in the 1930s) is of course  supposedly pure, but actually consists mostly of "harmless" filler . It is usually taken with a small glass of water.

The orange was - in the eyes of the Modernist 1930s - an impure source of vitamin c. The orange consisted mostly of harmless filler (pulp fibre and a great taste) and about the same amount of water as needed to fill a small glass.

Despite being "impure", a whole (100mg)  orange a day would actually be more healthy for you than taking half (50 mg) of a "pure" pill every day.

All the body craves is its fix of 100 mg of the "C" a day , not whether human minds consider that vitamin c to be pure or impure.

Unless the vitamin c is bound to something that renders it biologically inactive, the body considers it as fully pure and effective and dismisses what sort of filler and water it chanced to come bundled with.

It was exactly same with the human bodies our two wartime Aussie doctors Duhig and Florey had taken a sacred oath to protect.

Heroic penicillin at its best ...

From twelve one liter flasks growing penicillium fungus in his Brisbane hospital lab , in late 1943, Dr James Dunhig got 2500 cc of penicillin juice, averaging at best five biologically active units of penicillin per cc , or about 12,500 units in total.

This crude, impure, liquid was strained but not processed - only kept chilled.

It was almost immediately put into a 42 year dying mother, a patient of Dr Geaney, in various sizes of IV doses (some as large at 600 cc) over a number of days -- and yet this impure medicine saved her life and home she went to her grateful and astonished family.

Dr Florey,originally from Adelaide, from the same 2500 cc of starting penicillin juice grown in his Oxford university lab in late 1943, also started off with 12,500 units of crude, unprocessed, penicillin.

But he chose to refine it over and over and over and over again, losing and destroying most of the penicillin in the long process.

Finally he ended up with a very little pile of relatively pure powder : one tiny mg of dried penicillin,  assaying about 1250 units of biological activity.

But you can't inject dry powder - no matter how pure - into a patient, so some of that oh so expensively extracted water had to be mixed again with the dry penicillin,  if it was to be usefully injected  in a dying patient.

Non-heroic penicillin, at its worst ...

But it wasn't - it was given instead to chemists, to be deliberately destroyed , all to make a more accurate assessment of penicillin's structure by examining its various sub components.

Then (in the middle of a deadly world war)  public domain penicillin could finally - profitably -  be synthetically analogued and  patented.

Just as well that Florey wasn't moved to waste any of his preciously pure penicillin on a dying woman, because 1250 units of penicillin , no matter how pure, couldn't save most dying adults but 12,500 units of impure penicillin sometimes did.

It is as I say, a classic example of the old saying that 'an whole impure orange a day will keep the doctor away, but half a pill of pure little white pill will not' ...